Cardiovascular disease is the leading cause of death in the United States and in most developed countries. Long-term aspirin therapy reduces the risk of subsequent myocardial infarction (MI), stroke and vascular death among patients with a wide range of prior manifestations of cardiovascular disease. Aspirin is effective in the prevention of coronary artery disease (CAD) and stroke and thus can be used as a primary prevention of CAD. Among patients with prior MI, stroke, transient ischemic attacks (TIAs), unstable angina, angioplasty and acute coronary syndromes, immediate aspirin therapy provides significant benefit in reducing death, recurrent MI, TIA's or stroke. The benefits are seen in men and women, the elderly of both sexes as well as patients with risk factors for CAD, hypertension and diabetes.
The most widely employed dose of ASA in primary as well as the secondary prevention trials is a dose of 325 mg/day. Dosages in a range of 75 to 325 mg per/day have been found effective in clinical trials. The survival benefits of immediate oral aspirin therapy for an acute MI or stroke are seen during the first month and persist for several years. Oral ASA therapy though has limitations. It cannot be given to intubated patients, has slow onset of action, and in emergency, is often given to a patient to chew with the potential of GI upset leading to emesis or a severe burning of the oral mucosa and upper esophagus. Efforts have been made to develop a parenteral formulation of aspirin. Aspirin has poor solubility in water at 25° C. In an attempt to prepare an aqueous formulation of aspirin, aspirin was converted to its lysine salt. Lysine acetylsalicylate (trade name Aspegic or Aspisol) is the lysine salt of aspirin and is readily water soluble and this compound has been used as an injectable form of aspirin in Europe. However, a considerably larger dose is needed to be given, since it was found that 900 mg of lysine salt of aspirin is approximately equivalent to 500 mg of aspirin. This salt of ASA needs to be metabolized to salicylic acid for its biologic actions. The drug is delivered to target organs, where aspirin is released for its pharmacological effects. Studies with this formulation suggested that the lysine salt was effective in the treatment of acute migraine headaches. The shortest half life after IV administration was 7.5 minutes. Metabolism and hydrolysis to salicylic acid is rapid. Limiting the utility of the lysine ASA is the sensitivity it can cause that can lead to anaphylactic shock in patients with an incidence of up to 5%. This adversity limits the utility of the lysine ASA preparation for clinical use.